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Breast cancer immunotherapy

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https://www.readbyqxmd.com/read/28315060/results-of-a-phase-ib-trial-of-combination-immunotherapy-with-a-cd8-%C3%A2-t-cell-eliciting-vaccine-and-trastuzumab-in-breast-cancer-patients
#1
G Travis Clifton, Jennifer K Litton, Karen Arrington, Sathibalan Ponniah, Nuhad K Ibrahim, Victor Gall, Gheath Alatrash, George E Peoples, Elizabeth A Mittendorf
BACKGROUND: CD8+ T cell-eliciting vaccines are being investigated in breast cancer patients. Preclinical data showed that trastuzumab increases the susceptibility of tumor cells to lysis by vaccine-generated CD8+ T cells, suggesting potential benefit of a combination immunotherapy strategy. The current trial was undertaken to demonstrate the safety of this approach. METHODS: This study was designed as a dose-escalation trial enrolling clinically disease-free, human leukocyte antigen A2+ or A3+ , human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients...
March 17, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28290464/blocking-the-recruitment-of-naive-cd4-t-cells-reverses-immunosuppression-in-breast-cancer
#2
Shicheng Su, Jianyou Liao, Jiang Liu, Di Huang, Chonghua He, Fei Chen, LinBing Yang, Wei Wu, Jianing Chen, Ling Lin, Yunjie Zeng, Nengtai Ouyang, Xiuying Cui, Herui Yao, Fengxi Su, Jian-Dong Huang, Judy Lieberman, Qiang Liu, Erwei Song
The origin of tumor-infiltrating Tregs, critical mediators of tumor immunosuppression, is unclear. Here, we show that tumor-infiltrating naive CD4(+) T cells and Tregs in human breast cancer have overlapping TCR repertoires, while hardly overlap with circulating Tregs, suggesting that intratumoral Tregs mainly develop from naive T cells in situ rather than from recruited Tregs. Furthermore, the abundance of naive CD4(+) T cells and Tregs is closely correlated, both indicating poor prognosis for breast cancer patients...
March 14, 2017: Cell Research
https://www.readbyqxmd.com/read/28276425/the-shc1-adaptor-simultaneously-balances-stat1-and-stat3-activity-to-promote-breast-cancer-immune-suppression
#3
Ryuhjin Ahn, Valérie Sabourin, Alicia M Bolt, Steven Hébert, Stephanie Totten, Nicolas De Jay, Maria Carolina Festa, Yoon Kow Young, Young Kyuen Im, Tony Pawson, Antonis E Koromilas, William J Muller, Koren K Mann, Claudia L Kleinman, Josie Ursini-Siegel
Tyrosine kinase signalling within cancer cells is central to the establishment of an immunosuppressive microenvironment. Although tyrosine kinase inhibitors act, in part, to augment adaptive immunity, the increased heterogeneity and functional redundancy of the tyrosine kinome is a hurdle to achieving durable responses to immunotherapies. We previously identified the Shc1 (ShcA) scaffold, a central regulator of tyrosine kinase signalling, as essential for promoting breast cancer immune suppression. Herein we show that the ShcA pathway simultaneously activates STAT3 immunosuppressive signals and impairs STAT1-driven immune surveillance in breast cancer cells...
March 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28274891/roles-of-cancer-testis-antigens-ctas-in-breast-cancer
#4
Yongfei Li, Jun Li, Yanhong Zhang, Yifan Wang, Jiahui Chu, Chunxiao Sun, Ziyi Fu, Yi Huang, Yongmei Yin
Breast cancer is the most common cancer diagnosed and is the second leading cause of cancer death among women in the US. For breast cancer, early diagnosis and efficient therapy remains a significant clinical challenge. Therefore, it is necessary to identify novel tumor associated molecules to target for biomarker development and immunotherapy. In this regard, cancer testis antigens (CTAs) have emerged as a potential clinical biomarker targeting immunotherapy for various malignancies due to the nature of its characteristics...
March 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28264810/promoter-methylation-modulates-indoleamine-2-3-dioxygenase-1-induction-by-activated-t-cells-in-human-breast-cancers
#5
Satish K Noonepalle, Franklin Gu, Eun-Joon Lee, Jeong-Hyeon Choi, Qimei Han, Jaejik Kim, Maria Ouzounova, Austin Y Shull, Lirong Pei, Pei-Yin Hsu, Ravindra Kohle, Fang Shi, Jiseok Choi, Katie Chiou, Tim H M Huang, Hasan Korkaya, Libin Deng, Hong-Bo Xin, Shuang Huang, Muthusamy Thangaraju, Arun Sreekumar, Stefan Ambs, Shou-Ching Tang, David H Munn, Huidong Shi
Triple-negative breast cancer (TNBC) cells are modulated in reaction to tumor-infiltrating lymphocytes. However, their specific responses to this immune pressure are unknown. In order to address this question, we first used mRNA sequencing to compare the immunophenotype of the TNBC cell line MDA-MB-231 and the luminal breast cancer cell line MCF7 after both were cocultured with activated human T cells. Despite similarities in the cytokine-induced immune signatures of the two cell lines, MDA-MD-231 cells were able to transcribe more IDO1 than MCF7 cells...
March 6, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28254787/serine-proteases-enhance-immunogenic-antigen-presentation-on-lung-cancer-cells
#6
Haley L Peters, Satyendra C Tripathi, Celine Kerros, Hiroyuki Katayama, Haven R Garber, Lisa S St John, Lorenzo Federico, Ismail M Meraz, Jack A Roth, Boris Sepesi, Mourad Majidi, Kathryn Ruisaard, Karen Clise-Dwyer, Jason Roszik, Don L Gibbons, John Heymach, Stephen G Swisher, Chantale Bernantchez, Gheath Alatrash, Samir M Hanash, Jeffrey J Molldrem
Immunotherapies targeting immune checkpoints have proven efficacious in reducing the burden of lung cancer in patients; however, the antigenic targets of these re-invigorated T cells remain poorly defined. Lung cancer tumors contain tumor-associated macrophages (TAM) and neutrophils, which release the serine proteases neutrophil elastase (NE) and proteinase 3 (P3) into the tumor microenvironment. NE and P3 shape the antitumor adaptive immune response in breast cancer and melanoma. In this report, we demonstrate that lung cancer cells cross-presented the tumor-associated antigen PR1, derived from NE and P3...
March 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28250045/correction-deep-sequencing-of-t-cell-receptor-dna-as-a-biomarker-of-clonally-expanded-tils-in-breast-cancer-after-immunotherapy
#7
(no author information available yet)
No abstract text is available yet for this article.
March 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28224210/tumor-specific-regulatory-t-cells-in-the-bone-marrow-of-breast-cancer-patients-selectively-upregulate-the-emigration-receptor-s1p1
#8
Anchana Rathinasamy, Christoph Domschke, Yingzi Ge, Hans-Henning Böhm, Steffen Dettling, David Jansen, Felix Lasitschka, Ludmila Umansky, Markus H Gräler, Jennifer Hartmann, Christel Herold-Mende, Florian Schuetz, Philipp Beckhove
Regulatory T cells (Treg) hamper anti-tumor T-cell responses resulting in reduced survival and failure of cancer immunotherapy. Among lymphoid organs, the bone marrow (BM) is a major site of Treg residence and recirculation. However, the process governing the emigration of Treg from BM into the circulation remains elusive. We here show that breast cancer patients harbour reduced Treg frequencies in the BM as compared to healthy individuals or the blood. This was particularly the case for tumor antigen-specific Treg which were quantified by MHCII tumor peptide loaded tetramers...
February 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28216374/yin-yang-effect-of-tumor-infiltrating-b-cells-in-breast-cancer-from-mechanism-to-immunotherapy
#9
Zhigang Zhang, Ying Zhu, Zhen Wang, Ting Zhang, Pin Wu, Jian Huang
Breast cancer cells secrete chemokines, such as CXCL13, and antigens or express high endothelial venules, attracting B cells to infiltrate into the tumor microenvironment and play a "yin-yang" effect. They not only enhance the anti-tumor immune effect via secreting antibodies and influencing the Fas/FasL, CXCR4/CXCL12 and perforin pathways but they also promote the tumor to form a suppressive milieu by producing immunomodulatory factors and cytokines or using cell-to-cell education to induce the generation of Tregs or myeloid-derived suppressor cells (MDSCs)...
February 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28197375/tumor-infiltrating-lymphocyte-composition-organization-and-pd-1-pd-l1-expression-are-linked-in-breast-cancer
#10
Laurence Buisseret, Soizic Garaud, Alexandre de Wind, Gert Van den Eynden, Anais Boisson, Cinzia Solinas, Chunyan Gu-Trantien, Céline Naveaux, Jean-Nicolas Lodewyckx, Hugues Duvillier, Ligia Craciun, Isabelle Veys, Denis Larsimont, Martine Piccart-Gebhart, John Stagg, Christos Sotiriou, Karen Willard-Gallo
The clinical relevance of tumor-infiltrating lymphocytes (TIL) in breast cancer (BC) has been clearly established by their demonstrated correlation with long-term positive outcomes. Nevertheless, the relationship between protective immunity, observed in some patients, and critical features of the infiltrate remains unresolved. This study examined TIL density, composition and organization together with PD-1 and PD-L1 expression in freshly collected and paraffin-embedded tissues from 125 patients with invasive primary BC...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28193698/the-innate-and-adaptive-infiltrating-immune-systems-as-targets-for-breast-cancer-immunotherapy
#11
Andrew Mk Law, Elgene Lim, Christopher Ormandy, David Gallego-Ortega
A cancer cell-centric view has long dominated the field of cancer biology. Research efforts have focussed on aberrant cancer cell signalling pathways and on changes to cancer cell DNA. Mounting evidence demonstrates that many cancer-associated cell types within the tumour stroma co-evolve and support tumour growth and development, greatly modifying cancer cell behaviour, facilitating invasion and metastasis, and controlling dormancy and sensitivity to drug therapy. Thus, these stromal cells represent potential targets for cancer therapy...
February 13, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28178709/neoplastic-meningitis-due-to-lung-breast-and-melanoma-metastases
#12
REVIEW
Emilie Le Rhun, Sophie Taillibert, Marc C Chamberlain
BACKGROUND: Neoplastic meningitis, a central nervous system (CNS) complication of cancer metastatic to the meninges and cerebrospinal fluid (CSF), is relevant to oncologists due to the impact of the disease on patient quality of life and survival rates. METHODS: A review of the literature of articles published in English was conducted with regard to neoplastic meningitis. RESULTS: The incidence of neoplastic meningitis is increasing because patients with cancer are surviving longer in part because of the use of novel therapies with poor CNS penetration...
January 2017: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/28165048/expression-of-human-endogenous-retrovirus-k-is-strongly-associated-with-the-basal-like-breast-cancer-phenotype
#13
Gary L Johanning, Gabriel G Malouf, Xiaofeng Zheng, Francisco J Esteva, John N Weinstein, Feng Wang-Johanning, Xiaoping Su
Human endogenous retroviruses (HERVs), which make up approximately 8% of the human genome, are overexpressed in some breast cancer cells and tissues but without regard to cancer subtype. We, therefore, analyzed TCGA RNA-Seq data to evaluate differences in expression of the HERV-K family in breast cancers of the various subtypes. Four HERV-K loci on different chromosomes were analyzed in basal, Her2E, LumA, and LumB breast cancer subtypes of 512 breast cancer patients with invasive ductal carcinoma (IDC). The results for all four loci showed higher HERV-K expression in the basal subtype, suggesting similar mechanisms of regulation regardless of locus...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28162837/immunotherapy-in-breast-cancer-an-introduction
#14
Mary L Disis, Sasha E Stanton
The field of breast cancer immunology has progressed tremendously over the last decade. Twenty years ago immunotherapy was not considered for the treatment of breast cancers because breast cancer was not considered immunogenic. Today we know that most patients with breast cancer have some evidence of an adaptive immune response against their tumors, detectable either in the peripheral blood or in the tumor. Moreover, immunity to breast cancer begins at the earliest stages of the disease, in some patients prior to diagnosis...
February 3, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28160557/cancer-associated-oxidoreductase-ero1-%C3%AE-promotes-immune-escape-through-up-regulation-of-pd-l1-in-human-breast-cancer
#15
Tsutomu Tanaka, Goro Kutomi, Toshimitsu Kajiwara, Kazuharu Kukita, Vitaly Kochin, Takayuki Kanaseki, Tomohide Tsukahara, Yoshihiko Hirohashi, Toshihiko Torigoe, Yoshiharu Okamoto, Koichi Hirata, Noriyuki Sato, Yasuaki Tamura
Many human cancers have been reported to have enhanced expression of the immune checkpoint molecule programmed death-ligand 1 (PD-L1), which binds to programmed cell death-1 (PD-1) expressed on immune cells. PD-L1/PD-1 plays a role in inhibition of antitumor immunity by inducing T cell apoptosis and tolerance. Thus, it is crucial to elucidate mechanisms of PD-L1 expression on cancer cells. ERO1-α is an oxidase located in the endoplasmic reticulum. It is overexpressed in a variety of tumor types and it plays a role in disulfide bond formation in collaboration with PDI...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28159402/-evaluation-of-tumor-infiltrating-lymphocytes-in-breast-cancer-how-to-use-the-2014%C3%A2-international-guidelines
#16
Natacha Joyon, Manal Kordahi, Cécile Blanc-Fournier, Magali Lacroix-Triki
With the major development of immunotherapies, evaluation of the immune response associated to cancer has become the new challenge for pathologists. In breast cancer, this perspective has been notably anticipated by the recent publication, in 2014, of international guidelines for assessment of tumor-infiltrating lymphocytes (TILs), on routine haematoxylin-eosin stains. This technical article aims at reviewing the main key points and different steps in evaluation of tumor-infiltrating lymphocytes, in order to allow an easy implementation of this putative biomarker in routine practice...
February 2017: Annales de Pathologie
https://www.readbyqxmd.com/read/28143792/2003-2013-a-valuable-study-autologous-tumor-lysate-pulsed-dendritic-cell-immunotherapy-with-cytokine-induced-killer-cells-improves-survival-in-stage-iv-breast-cancer
#17
Mao Lin, Shuzhen Liang, Feng Jiang, Jiongyuan Xu, Weibing Zhu, Wei Qian, Yong Hu, Zhanchun Zhou, Jibing Chen, Lizhi Niu, Kecheng Xu, Youyong Lv
Dendritic cells (DCs) and cytokine-induced killer (CIK) cells have both shown activity as immunotherapy in some malignancies. Our aim was to prospective assess the effect of this immunotherapy in patients with stage IV breast cancer. Between Aug 2003 and Dec 2013, we collected 368 patients who met inclusion criteria and divided into immunotherapy group (treatment group: 188 patients) and chemotherapy group (control group: 180 patients). DCs were prepared from the mononuclear cells isolated from patients in the treatment group using IL-2/GM-CSF and were loaded with tumour antigens; CIK cells were prepared by incubating peripheral blood lymphocytes with IL-2, IFN-γ, and CD3 antibodies...
March 2017: Immunology Letters
https://www.readbyqxmd.com/read/28123606/strong-correlation-of-indoleamine-2-3-dioxygenase-1-expression-with-basal-like-phenotype-and-increased-lymphocytic-infiltration-in-triple-negative-breast-cancer
#18
Sewha Kim, Sanghui Park, Min Sun Cho, Woosung Lim, Byung-In Moon, Sun Hee Sung
Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme involved in tumor immune escape. Blockade of the IDO1 pathway is an emerging modality of cancer immunotherapy. Triple-negative breast cancer (TNBC) lacks established therapeutic targets and may be a good candidate for this novel immunotherapeutic agent. The purpose of this study was to evaluate the clinicopathologic characteristics of the IDO1-expressing TNBC subset. A tissue microarray was constructed from 200 patients with TNBC. Immunohistochemistry (IHC) for IDO1 and TNBC molecular subtype-surrogate markers (AR, GCDFP-15, claudin-3, E-cadherin, CK5/6, and EGFR) was performed using this tissue microarray...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28112278/cobimetinib-inhibiting-mek1-2-in-braf-v600-mutant-melanoma
#19
REVIEW
A Jimeno, J R Eagles
Historically, metastatic melanoma has had extremely poor survival outcomes. The outlook, however, is rapidly changing as new molecularly targeted therapies have vastly improved patient outcomes. One such therapy is the potent mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor cobimetinib. Recently, cobimetinib was approved for the treatment of metastatic or unresectable melanoma with serine/threonine-protein kinase B-raf (BRAF) V600E or V600K mutations when used in combination with the BRAF inhibitor vemurafenib...
November 2016: Drugs of Today
https://www.readbyqxmd.com/read/28107571/increased-pd-l1-expression-in-breast-and-colon-cancer-stem-cells
#20
Yanheng Wu, Mingshui Chen, Peihong Wu, Chen Chen, Zhi Ping Xu, Wenyi Gu
Here we report the expression of programmed cell death ligand 1/2 (PD-L1/L2) in breast and colon cancer stem cells (CSCs). The stemness of these cells was confirmed by their surface markers. Using flow cytometry analysis we demonstrated that PD-L1 expression was higher in CSCs of both cancers compared to non-stem like cancer cells. Consistent with this, detection of cellular PD-L1 proteins by Western blot assay also showed increased PD-L1 protein in CSCs. In contrast, only trance amounts of PD-L2 were detected in CSCs of both cancers...
January 20, 2017: Clinical and Experimental Pharmacology & Physiology
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